1. Field of the Invention
The present invention relates to an improved process for producing L-phenylalanine methyl ester (hereinafter "PM") and .alpha.-L-aspartyl-L-phenylalanine methyl ester (hereinafter ".alpha.-APM"), and more particularly to, a process for the preparation of .alpha.-APM in high yield, which is a sweetening agent called "ASPARTAME."
2. Description of the Prior Art
There are many known large scale methods in the art for the production of .alpha.-APM using L-phenylalanine. For example, U.S. Pat. No. 3,786,039 discloses a method for the production of .alpha.-APM by the use of N-protected-L-aspartic anhydride and the lower alkyl ester of L-phenylalanine utilizing certain organic solvents. U.S. Pat. Nos. 4,071,511 and 4,684,745 disclose methods for the production of .alpha.-APM by the use of N-formyl aspartic anhydride and L-phenylalanine methyl ester to produce N-formyl-L-aspartyl-L-phenylalanine methyl ester and recovering the final product, .alpha.-APM, as the hydrochloric acid salt. U.S. Pat. No. 3,492,131 and U.S. Pat. No. 4,680,403 disclose methods for the production of PM by the use of sulfuric acid and hydrochloric acid, respectively, as the esterification catalyst. However, such prior art methods suffer from a number of disadvantages such as, for example, (a) they exhibit a lower yield; (b) since water is formed by esterification, this step takes a long time and produces an impure final product which contains, for example, .alpha.,.beta.-L-aspartyl-L-phenylalanine dimethylester (hereinafter ".alpha.,.beta.-MAPM"), by-product.